Most current studies are centered on six Mycoplasma species of humans. Some of these isolates represent completely new and recently identified organisms in the urogential tract of AIDS patients, while other mycoplasmas are previously known species that have apparently assumed new roles in association with human disease or are occurring in previously unknown tissue sites in man. Further evidence has been obtained for an important role of Mycoplasma genitalium in mixed infections with M. pneumoniae. Isolation of both mycoplasmas was made in our laboratory from synovial fluid of a patient with acute respiratory disease, and who subsequently developed polyarthritis in the wrist and knee joints. Immunoblots of the patient's serum against purified adhesin proteins from both mycoplasmas showed an exaggerated immune response to the adhesin protein (140 KDa) of M. genitalium, over than observed with the P1 (168 KDa) adhesin protein of M. pneumoniae. We believe the occurrence of M. genitalium in the joint fluids and the unusual immune response to the attachment protein of the organism offers further support for the role of the organism in human disease. Additional studies have been done on the molecular and genetic features of a group of new wall-free mollicutes (mycoplasmas). These organisms, primarily of insect origin, have been definined as new species in the genus Mesoplasma. The organisms lack a growth requirement for sterol, and differ significantly from other sterol- nonrequiring mollicutes (acholeplasmas). They have genome sizes smaller than acholeplasmas, use UGA as a tryptophan codon rather than as a stop signal, and possess enzyme II of the phophotransferase sugar transport system (which is lacking in acholeplasmas). A phylogenetic analysis, based upon a comparison of 16S rRNA sequences, among the new organisms and other members of the class Mollicutes supports our taxonomic proposals.